Rheumatoid arthritis and the era of biologic therapy.

Biologic disease modifying anti-rheumatic drugs have transformed the management of rheumatoid arthritis (RA) since their introduction into clinical practice over a decade ago. Following large-scale clinical trials, a number of biologics, with different mechanisms of action, have been licensed for the condition. In this review, we will summarise the current evidence for biologic use in RA with an emphasis on their efficacy and tolerability. In addition, we will provide a commentary on the current limitations and unmet needs in this area and discuss the future of biologic intervention.

Targeting CVD risk in chronic connective tissue disease.

Chronic inflammatory rheumatological conditions are associated with an increased burden of cardiovascular disease (CVD). In both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) most excess mortality is cardiovascular. Increased CVD risk is also associated with psoriatic arthritis, ankylosing spondylitis, antiphospholipid syndrome and systemic sclerosis. Several studies report that CVD mortality increases early in disease in RA, with increased risk of MI within one year and increased risk of hospital admission for CVD within seven years of diagnosis. A linear association has been demonstrated between subclinical carotid atherosclerosis and raised inflammatory markers. SLE is associated with 2-10 times the risk of a CVD event compared with the general population. CVD is now a leading cause of morbidity and mortality in SLE. Antiphospholipid antibodies are associated with accelerated atherosclerosis, as well as thromboses. Atherogenesis in the context of autoimmune disease results from a complex interplay between traditional risk factors, disease-specific factors and drug-related adverse effects. Chronic inflammation itself modifies the lipid profile.

Early diagnosis crucial in ankylosing spondylitis.

Ankylosing spondylitis (AS) is an inflammatory autoimmune disorder that predominantly affects the spine. If untreated it may cause significant morbidity. Early diagnosis is particularly important as newer therapies are able to contain this condition and even induce remission. AS affects about 0.2-0.5% of the population. It is at least twice as common in men and most often manifests in the third to fifth decades. It is estimated that up to 5% of patients with chronic lower back pain in primary care have inflammatory disease. Although only 1% of patients with HLA-B27 develop AS, 90-95% of patients with AS are positive for HLA-B27. Immune dysfunction is the hallmark of this condition and it may be triggered by infection. The primary site of inflammation in AS is the entheses, the sites of insertion of tendons and ligaments into bone. If the inflammation remains untreated, there is resultant fibrosis and ultimately ossification at the entheseal sites. AS should be suspected in patients who report back pain and stiffness with rest, especially in the morning, which improves with exercise. Although the condition affects both the sacroiliac joints, a proportion of patients report pain radiating into the buttocks which may be unilateral or alternate, particularly in the early stages. In addition to the spine, large joint synovitis may develop as well as features of entheseal involvement. New classification criteria take into account early sacroiliitis evident on MRI scan and allow a diagnosis to be made far earlier than was previously possible. A proportion of patients respond well to NSAIDs coupled with a structured physiotherapy and exercise programme. However, about half these patients need escalation to biologic therapy. Patients with a suspected diagnosis should be referred to secondary care in order to confirm the diagnosis and commence treatment.

Indispensable or intolerable? Methotrexate in patients with rheumatoid and psoriatic arthritis: a retrospective review of discontinuation rates from a large UK cohort.

Methotrexate (MTX) has become the first-line treatment for rheumatoid (RA) and psoriatic arthritis (PsA); however, few studies have focused on its tolerability. The objective of our analyses was to study RA and PsA patients in whom MTX was discontinued, the reasons for this and the duration of MTX treatment prior to withdrawal. A retrospective electronic database review was undertaken to identify all patients who had received MTX for RA or PsA. Patients who had discontinued MTX were then identified, and the reasons for this were categorised. The duration of MTX treatment was assessed in those who had stopped treatment due to intolerability. A total of 1,257 patients who had received MTX were identified [762 (61 %) RA and 193 (15 %) PsA]. MTX had been stopped in 260 (34 %) patients with RA and 71 (36 %) patients with PsA most commonly due to gastrointestinal intolerability. The median duration of MTX treatment was 10 months in both groups, mean duration 21 and 18.6 months in RA and PsA groups, respectively. Overall, one third of patients with RA and PsA stop MTX most commonly due to poor tolerability. In the context of chronic disease, the median duration of treatment is short (10 months). Our analysis did not include patients who suffer from side effects but continue therapy; thus, the magnitude of the problem may be substantially greater therefore as poor tolerability impacts treatment adherence.

Drug adherence to biologic DMARDS with a special emphasis on the benefits of subcutaneous abatacept.

Major advances in drug development have led to the introduction of biologic disease- modifying drugs for the treatment of rheumatoid arthritis, which has resulted in unprecedented improvement in outcomes for many patients. These agents have been found to be effective in reducing clinical signs and symptoms, improving radiological damage, quality of life, and functionality, and have also been found to have an acceptable safety profile. Despite this, drug adherence is unknown, which has huge health care and health-economic implications. Local and national guidelines exist for the use of biologics; however, its varied use is widespread. Although this may in part reflect differences in prescribing behavior, patient preference plays a key role. In this review we will explore the factors that contribute to patient preference for, and adherence to, biologic therapy for rheumatoid arthritis with emphasis on the subcutaneous preparation of abatacept, a T-cell costimulatory molecule blocker. Overall, subcutaneous administration is preferred by patients and this may well improve drug adherence.